We have recently identified two new nonhistone protein antigens in mouse. One of them (NHP-N) is present in nuclear fractions from normal liver, but not in those of hepatomas, while the other (NHP-H) is preferentially expressed inn hepatomas. NHP-N has been purified to homogeneity. It is an 18,000 dalton protein with a single polypeptide chain. It has an isoelectric point o 4.5, it is soluble in perchloric acid, but not contain carbohydrate. We now propose to isolate NHP-H and prepare immunochemical reagents for the detection of NHP-H by immunofluorescence and for their quantitative measurement by radioimmunoassay. These tests will be used to study the subcellular and tissue distribution of these antigens in normal liver and other tissues, regenerating and fetal liver, transplantable and spontaneous hepatomas and livers obtained during early stages of spontaneous carcinogenesis in C3H mice. We also propose to try to identify the corresponding proteins in humans. The preferential expression of these proteins in the nomal (NHP-N) or (NHP-H) cells and their nuclear localization suggests that they may play a roll in the transformation process or in the maintenance of the transformed state. Few nuclear proteins have been isolated so far and none of them has been characterized in terms of their expression during carcinogenesis. This research should therefore be a significant addition to the existing body of knowledge on nuclear proteins. NHP-H may become a useful tumor marker for immunodiagnosis.